NDUS6_MOUSE
ID NDUS6_MOUSE Reviewed; 116 AA.
AC P52503; Q5M9J7;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 2.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial;
DE AltName: Full=Complex I-13kD-A;
DE Short=CI-13kD-A;
DE AltName: Full=NADH-ubiquinone oxidoreductase 13 kDa-A subunit;
DE Flags: Precursor;
GN Name=Ndufs6; Synonyms=Ip13;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 34-113.
RC STRAIN=CD-1;
RX PubMed=7607554; DOI=10.1016/0378-1119(95)00029-6;
RA Watson J.D., Beckett-Jones B., Roy R.N., Green N.C., Flynn T.G.;
RT "Genomic sequence, structural organization and evolutionary conservation of
RT the 13.2-kDa subunit of rat NADH:ubiquinone oxidoreductase.";
RL Gene 158:275-280(1995).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22474353; DOI=10.1073/pnas.1113987109;
RA Ke B.X., Pepe S., Grubb D.R., Komen J.C., Laskowski A., Rodda F.A.,
RA Hardman B.M., Pitt J.J., Ryan M.T., Lazarou M., Koleff J., Cheung M.M.,
RA Smolich J.J., Thorburn D.R.;
RT "Tissue-specific splicing of an Ndufs6 gene-trap insertion generates a
RT mitochondrial complex I deficiency-specific cardiomyopathy.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:6165-6170(2012).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-90 AND LYS-112, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
CC -!- FUNCTION: Accessory subunit of the mitochondrial membrane respiratory
CC chain NADH dehydrogenase (Complex I), that is believed not to be
CC involved in catalysis. Complex I functions in the transfer of electrons
CC from NADH to the respiratory chain. The immediate electron acceptor for
CC the enzyme is believed to be ubiquinone.
CC {ECO:0000250|UniProtKB:O75380}.
CC -!- SUBUNIT: Mammalian complex I is composed of 45 different subunits. This
CC is a component of the iron-sulfur (IP) fragment of the enzyme.
CC {ECO:0000269|PubMed:22474353}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000305|PubMed:22474353}; Peripheral membrane protein
CC {ECO:0000305}; Matrix side {ECO:0000305}.
CC -!- DISRUPTION PHENOTYPE: Male and female mice are fertile but produce
CC smaller litters and pups have a lower neonatal survival rate
CC (PubMed:22474353). While mice are normal during the first 4 months of
CC life, they are prone to rapid onset weight loss and sudden death after
CC this period (PubMed:22474353). They display cardiomyopathy associated
CC with a doubling of heart weight, impaired systolic function and a
CC reduction in functional capacity (PubMed:22474353). Males are most
CC severely affected, with a propensity to develop cardiac failure and
CC diminished survival after 4 months of age (PubMed:22474353). Defects
CC are due to membrane respiratory chain NADH dehydrogenase (Complex I)
CC deficiency (PubMed:22474353). In the knockout experiment described
CC above, mice show a complete knockout of Ndufs6 subunit in heart
CC resulting in marked complex I deficiency, but small amounts of wild-
CC type Ndufs6 mRNA are still present in other tissues, probably due to
CC tissue-specific mRNA splicing, resulting in milder complex I defects
CC (PubMed:22474353). {ECO:0000269|PubMed:22474353}.
CC -!- SIMILARITY: Belongs to the complex I NDUFS6 subunit family.
CC {ECO:0000305}.
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DR EMBL; BC086933; AAH86933.1; -; mRNA.
DR EMBL; L38438; AAB64010.1; -; Genomic_DNA.
DR CCDS; CCDS26630.1; -.
DR RefSeq; NP_035018.1; NM_010888.2.
DR PDB; 6G2J; EM; 3.30 A; R=1-116.
DR PDB; 6G72; EM; 3.90 A; R=1-116.
DR PDB; 6ZR2; EM; 3.10 A; R=1-116.
DR PDB; 6ZTQ; EM; 3.00 A; R=1-116.
DR PDB; 7AK5; EM; 3.17 A; R=1-114.
DR PDB; 7AK6; EM; 3.82 A; R=1-116.
DR PDB; 7B93; EM; 3.04 A; R=1-116.
DR PDB; 7PSA; EM; 3.40 A; R=1-116.
DR PDBsum; 6G2J; -.
DR PDBsum; 6G72; -.
DR PDBsum; 6ZR2; -.
DR PDBsum; 6ZTQ; -.
DR PDBsum; 7AK5; -.
DR PDBsum; 7AK6; -.
DR PDBsum; 7B93; -.
DR PDBsum; 7PSA; -.
DR AlphaFoldDB; P52503; -.
DR SMR; P52503; -.
DR BioGRID; 240437; 34.
DR ComplexPortal; CPX-266; Mitochondrial respiratory chain complex I.
DR CORUM; P52503; -.
DR IntAct; P52503; 3.
DR STRING; 10090.ENSMUSP00000022097; -.
DR iPTMnet; P52503; -.
DR PhosphoSitePlus; P52503; -.
DR SwissPalm; P52503; -.
DR EPD; P52503; -.
DR jPOST; P52503; -.
DR MaxQB; P52503; -.
DR PaxDb; P52503; -.
DR PeptideAtlas; P52503; -.
DR PRIDE; P52503; -.
DR ProteomicsDB; 293647; -.
DR Antibodypedia; 22354; 220 antibodies from 32 providers.
DR DNASU; 407785; -.
DR Ensembl; ENSMUST00000022097; ENSMUSP00000022097; ENSMUSG00000021606.
DR GeneID; 407785; -.
DR KEGG; mmu:407785; -.
DR UCSC; uc007rdh.2; mouse.
DR CTD; 4726; -.
DR MGI; MGI:107932; Ndufs6.
DR VEuPathDB; HostDB:ENSMUSG00000021606; -.
DR eggNOG; KOG3456; Eukaryota.
DR GeneTree; ENSGT00390000015775; -.
DR HOGENOM; CLU_083053_3_2_1; -.
DR InParanoid; P52503; -.
DR OrthoDB; 1641902at2759; -.
DR PhylomeDB; P52503; -.
DR TreeFam; TF315128; -.
DR Reactome; R-MMU-611105; Respiratory electron transport.
DR Reactome; R-MMU-6799198; Complex I biogenesis.
DR BioGRID-ORCS; 407785; 4 hits in 72 CRISPR screens.
DR ChiTaRS; Ndufs6; mouse.
DR PRO; PR:P52503; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; P52503; protein.
DR Bgee; ENSMUSG00000021606; Expressed in right kidney and 120 other tissues.
DR ExpressionAtlas; P52503; baseline and differential.
DR Genevisible; P52503; MM.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISO:MGI.
DR GO; GO:0005747; C:mitochondrial respiratory chain complex I; IDA:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0009060; P:aerobic respiration; IC:ComplexPortal.
DR GO; GO:0072359; P:circulatory system development; IMP:MGI.
DR GO; GO:0006631; P:fatty acid metabolic process; IMP:MGI.
DR GO; GO:0001822; P:kidney development; IMP:MGI.
DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; IBA:GO_Central.
DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:MGI.
DR GO; GO:0070584; P:mitochondrion morphogenesis; IMP:MGI.
DR GO; GO:0010259; P:multicellular organism aging; IMP:MGI.
DR GO; GO:0035264; P:multicellular organism growth; IMP:MGI.
DR GO; GO:0006936; P:muscle contraction; IMP:MGI.
DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; IC:ComplexPortal.
DR GO; GO:0061458; P:reproductive system development; IMP:MGI.
DR GO; GO:0022904; P:respiratory electron transport chain; IMP:MGI.
DR InterPro; IPR016668; NDUFS6.
DR InterPro; IPR019401; Znf_CHCC.
DR Pfam; PF10276; zf-CHCC; 1.
DR PIRSF; PIRSF016564; CI-13KD-A; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Electron transport; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Reference proteome; Respiratory chain;
KW Transit peptide; Transport.
FT TRANSIT 1..20
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT CHAIN 21..116
FT /note="NADH dehydrogenase [ubiquinone] iron-sulfur protein
FT 6, mitochondrial"
FT /id="PRO_0000043171"
FT MOD_RES 90
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 112
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT CONFLICT 37
FT /note="V -> VTM (in Ref. 2; AAB64010)"
FT /evidence="ECO:0000305"
FT CONFLICT 75
FT /note="R -> H (in Ref. 2; AAB64010)"
FT /evidence="ECO:0000305"
FT CONFLICT 85..87
FT /note="ALG -> SLV (in Ref. 2; AAB64010)"
FT /evidence="ECO:0000305"
FT CONFLICT 105
FT /note="G -> A (in Ref. 2; AAB64010)"
FT /evidence="ECO:0000305"
FT STRAND 26..28
FT /evidence="ECO:0007829|PDB:6G2J"
FT HELIX 43..48
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT HELIX 60..65
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT STRAND 70..79
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT STRAND 82..84
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT STRAND 91..94
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT STRAND 98..100
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT STRAND 105..107
FT /evidence="ECO:0007829|PDB:6ZTQ"
FT STRAND 111..113
FT /evidence="ECO:0007829|PDB:6ZTQ"
SQ SEQUENCE 116 AA; 13020 MW; 29C5FDCB491C4B2C CRC64;
MAAVLTFRRL LTLPRAARGF GVQVSPSGEK ITHTGQVYDE KDYRRVRFVD RQKEVNENFA
IDLIAQQPVN EVEHRIIACD GGGGALGHPK VYINLDKETK TGTCGYCGLQ FKQHHH
